Short-Term Ingestion of Essential Amino Acid Based Nutritional Supplements or Whey Protein Improves the Physical Function of Older Adults Independently of Gut Microbiome.

SCOPE: Dietary proteins and essential amino acids (EAAs) are the major nutritional supplements that support the growth and activity of gut microbes contributing to the wellbeing of their host. This study hypothesizes that daily supplementation of the diet with either EAAs or whey protein for 12 weeks would improve the gut microbiome of older adults. METHODS AND RESULTS: The stool samples are processed and subjected to Illumina-based 16S ribosomal ribonucleic acid (rRNA) gene amplicon sequencing. In both groups, the most abundant families are found in order of relative abundance included: Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, Prevotellaceae, Rikenellaceae, Enterobacteriaceae, Oscillospiraceae, Tannerellaceae, and Akkermansiaceae, which indicate that these subjects are able to maintain a same healthy microbial diversity in their guts. A significant finding is a reduction of proinflammatory cytokine, interleukin-18 (IL-18) in the EAAs group. It also uses the standard 6-min walking test (6MWT) as a measure of cardiopulmonary fitness. At the end of the study, the subjects in the EAAs group perform significantly better in the 6MWT as compared to the whey group. CONCLUSION: It seems plausible that the improved physical performance and reduced proinflammatory cytokine, IL-18 seen in the EAAs group, are independent of changes in gut microbiota.

Differential plasma protein expression after ingestion of essential amino acid-based dietary supplement verses whey protein in low physical functioning older adults.

In a recent randomized, double-blind, placebo-controlled trial, we were able to demonstrate the superiority of a dietary supplement composed of essential amino acids (EAAs) over whey protein, in older adults with low physical function. In this paper, we describe the comparative plasma protein expression in the same subject groups of EAAs vs whey. The plasma proteomics data was generated using SOMA scan assay. A total of twenty proteins were found to be differentially expressed in both groups with a 1.5-fold change. Notably, five proteins showed a significantly higher fold change expression in the EAA group which included adenylate kinase isoenzyme 1, casein kinase II 2-alpha, Nascent polypeptide-associated complex subunit alpha, peroxiredoxin-1, and peroxiredoxin-6. These five proteins might have played a significant role in providing energy for the improved cardiac and muscle strength of older adults with LPF. On the other hand, fifteen proteins showed slightly lower fold change expression in the EAA group. Some of these 15 proteins regulate metabolism and were found to be associated with inflammation or other comorbidities. Gene Ontology (GO) enrichment analysis showed the association of these proteins with several biological processes. Furthermore, protein-protein interaction network analysis also showed distinct networks between upregulated and downregulated proteins. In conclusion, the important biological roles of the upregulated proteins plus better physical function of participants in the EAAs vs whey group demonstrated that EAAs have the potential to improve muscle strength and physical function in older adults. This study was registered with ClinicalTrials.gov: NCT03424265 "Nutritional interventions in heart failure."

Disparity and Multimorbidity in Heart Failure Patients Over the Age of 80.

Background: Healthcare is currently struggling to provide access and coverage for an increasingly diverse aging population who frequently have multiple co-morbid conditions complicating their care and medical management. Methods: This retrospective study analyzed the prevalence and distribution of common co-morbid conditions (hypertension, dyslipidemia, dementia, and diabetes mellitus) in 316 elderly heart failure patients (age range 80-103; mean 87 ±4.9). Results: Chart review analysis showed a racial distribution of 65 African American versus 251 Caucasian patients (21 vs. 79%). Hypertension was comparable in both groups (98.5% African American vs. 92.4% Caucasian). Dyslipidemia, diabetes and dementia diagnoses were all approximately 20% higher in African American versus Caucasian patients. The concurrent presence of all four conditions was approximately three times more prevalent in African Americans (18.5%) versus Caucasians (7.2%). Conclusion: Our study is unique for studying disparity in octogenarian and nonagenarians residing in a rural setting. Our results also highlight the importance of making a special effort to engage older African American patients in seeking healthcare. In addition, strategies must be designed to reduce barriers that impede access and availability of resources and clinical care, especially in economically underserved regions of the country.

Quality Improvement in Delirium Health Literacy in Older Adult Patients and Their Caregivers Attending a Geriatric Clinic.

Background: Delirium is a common medical condition that is highly prevalent in older adults who are at increased risk for its development with any illness, post-surgery or during hospitalization. The purpose of our study was to evaluate the health literacy of older adult patients and their caregivers about delirium, offer a brief educational intervention, and reevaluate their knowledge post intervention. Materials and Methods: We conducted a quality improvement project, focused on delirium health literacy in older adult patients ≥60 years and their caregivers. Delirium knowledge of participants was evaluated in a pre-education survey after which they were given a delirium education booklet to read. A post-education delirium survey was conducted within 2-3 weeks of the educational intervention. Chi-square test was used to analyze the knowledge base of older adults. Results: The study population consisted of a total of 70 older adults who participated in pre-education (n=35) and post-education (n=35) surveys. Older adult patients and their caregivers had significant knowledge gaps about the potential causes or etiologies, risk factors, symptomatology, and prevention of delirium in the pre-education survey. After the educational intervention, in the post-education survey, there were overall improvements in knowledge base of older adults in differentiating delirium with dementia (43% vs 94%, p<0.01) recognizing signs and symptoms (77% vs 94%, p<0.05), complications (76% vs 100%, p<0.01) and identifying the etiological factors associated with delirium. Conclusion: The quality improvement project demonstrated that older adults and caregivers have significant knowledge deficits about the common condition of delirium. This study also demonstrated that older adults were able to improve their health literacy regarding delirium after the intervention. Appropriate education on delirium for patients and caregivers might help in earlier identification, prevention, and better overall management of delirium.

Does Superior Bone Health Promote a Longer Lifespan?

INTRODUCTION: Public health achievements throughout the last century have resulted in a steady increase in life expectancy. An emergent subset has distinguished themselves, living well beyond the ninth decade by avoiding or delaying the onset of most age-related diseases, including bone diseases and fractures. In this study, we evaluated the bone health of the oldest community-dwelling individuals living in rural Arkansas. METHODS: 299 patients aged ≥90 years were retrospectively reviewed for recorded fractures within 12 years prior to the investigation period. Records were also examined for medications and test results pertinent to bone health, including thyroid stimulating hormone, vitamin D levels, hematocrit, hemoglobin, body mass index, and bone densitometric values. RESULTS: 68 patients (23%) had at least one fracture documented, and 15 had >1 fracture. 40% of patients with fractures had osteoporosis and 28% had osteopenia, respectively. 232 patients (78%) had no documented fractures, and of these, only 18% had osteoporosis and 16% had osteopenia. No significant clinical markers were found among the very old to explain the relatively low occurrence of fractures. CONCLUSIONS: Patients over 90 years of age had an overall low prevalence of fractures and relative preservation of bone health, suggesting a preserved bone molecular profile in these individuals. Epigenetic factors and activity levels might also have favorably affected bone health. The low percentage of osteoporosis and fractures likely reduced the morbidity and mortality in this population, potentially contributing to their overall longevity.

Cardiovascular Health in Individuals with Exceptional Longevity Residing in Arkansas.

Cardiovascular disease is a common comorbidity associated with an aging population. However, there is a unique group of individuals whose age-defying qualities are still being investigated. This retrospective chart review analyzed various cardiac and metabolic health parameters to characterize the prevalence of heart failure and metabolic derangements in individuals aged 90 years old or older in central Arkansas. Only 236 of the 291 patients in our study cohort had blood pressures recorded. Of these, 50% had systolic blood pressures ≥140 mmHg. Additionally, 77% had pulse pressures ≥50 mmHg. Of the 96 patients with BNP data, 44% had values ≥300 pg/mL. There was a slight positive correlation between aging and HDL cholesterol, while there was a negative correlation between aging and both total cholesterol and LDL cholesterol. A majority of our patients had both elevated systolic blood pressures and elevated pulse pressures. A majority also had high BNP values, indicative of some degree of heart failure. Additionally, atrial fibrillation was a common arrhythmia identified on EKG. However, these oldest of the old patients had fewer documented metabolic derangements. These findings lay important groundwork for further investigation into lifestyle and genetic components that allow them to live exceptionally long with such comorbidities.

Potential Beneficial Effects of Dietary Protein Supplementation and Exercise on Functional Capacity in a Pilot Study of Individuals with Heart Failure with Preserved Ejection Fraction.

Approximately half of heart failure patients in the US have heart failure with preserved ejection fraction (HFpEF). HFpEF impairs physical performance and thus reduces quality of life. Increasing dietary protein intake can increase lean body mass and physical performance in healthy elderly individuals, but the effect of a high-quality protein supplement, with or without a structured exercise program, has not been investigated in HFpEF patients. Twenty-three obese elderly HFpEF patients with grade 1 or 2 diastolic dysfunction were randomized into three groups: control, protein supplementation alone, and protein plus exercise. Protein supplementation involved providing sufficient whey protein so that total intake was 1.2 g protein/kg/day. The exercise intervention was 2 days of hydrotherapy and 1 day of gym sessions per week under supervision of a fitness expert. Physical parameters and functional tests were performed at baseline and at 12 weeks. Protein supplementation alone failed to improve physical performance. However, when combined with light exercise, there was significant improvement in some (6-minute walk, 10 m walking speed, quadriceps strength), but not all, physical function measurements. The results of this pilot study suggest that further exploration of potential interactive effects between protein supplementation and light exercise in individuals with HFpEF is warranted.

Feasibility of Conducting a 6-month long Home-based Exercise Program with Protein Supplementation in Elderly Community-dwelling Individuals with Heart Failure.

OBJECTIVE: Cardiac cachexia is a condition associated with heart failure, particularly in the elderly, and is characterized by loss of muscle mass with or without the loss of fat mass. Approximately 15% of elderly heart failure patients will eventually develop cardiac cachexia; such a diagnosis is closely associated with high morbidity and increased mortality. While the mechanism(s) involved in the progression of cardiac cachexia is incompletely established, certain factors appear to be contributory. Dietary deficiencies, impaired bowel perfusion, and metabolic dysfunction all contribute to reduced muscle mass, increased muscle wasting, increased protein degradation, and reduced protein synthesis. Thus slowing or preventing the progression of cardiac cachexia relies heavily on dietary and exercise-based interventions in addition to standard heart failure treatments and medications. METHODS: The aim of the present study was to test the feasibility of an at-home exercise and nutrition intervention program in a population of elderly with heart failure, in an effort to determine whether dietary protein supplementation and increased physical activity may slow the progression, or prevent the onset, of cardiac cachexia. Frail elderly patients over the age of 55 with symptoms of heart failure from UAMS were enrolled in one of two groups, intervention or control. To assess the effect of protein supplementation and exercise on the development of cardiac cachexia, data on various measures of muscle quality, cardiovascular health, mental status, and quality of life were collected and analyzed from the two groups at the beginning and end of the study period. RESULTS: More than 50% of those who were initially enrolled actually completed the 6-month study. While both groups showed some improvement in their study measures, the protein and exercise group showed a greater tendency to improve than the control group by the end of the six months. CONCLUSION: These findings suggest that with a larger cohort, this intervention may show significant positive effects for elderly patients who are at risk of developing cardiac cachexia.

Hydration health literacy in the elderly.

BACKGROUND: Inadequate hydration in the elderly is associated with increased morbidity and mortality. However, few studies have addressed the knowledge of elderly individuals regarding hydration in health and disease. Gaps in health literacy have been identified as a critical component in health maintenance, and promoting health literacy should improve outcomes related to hydration associated illnesses in the elderly. METHODS: We administered an anonymous survey to community-dwelling elderly (n = 170) to gauge their hydration knowledge. RESULTS: About 56% of respondents reported consuming >6 glasses of fluid/day, whereas 9% reported drinking ≤3 glasses. About 60% of respondents overestimated the amount of fluid loss at which moderately severe dehydration symptoms occur, and 60% did not know fever can cause dehydration. Roughly 1/3 were not aware that fluid overload occurs in heart failure (35%) or kidney failure (32%). A majority of respondents were not aware that improper hydration or changes in hydration status can result in confusion, seizures, or death. CONCLUSIONS: Overall, our study demonstrated that there were significant deficiencies in hydration health literacy among elderly. Appropriate education and attention to hydration may improve quality of life, reduce hospitalizations and the economic burden related to hydration-associated morbidity and mortality.

Reversal of MicroRNA Dysregulation in an Animal Model of Pulmonary Hypertension.

BACKGROUND: Animals models have played an important role in enhancing our understanding of the pathogenesis of pulmonary arterial hypertension (PAH). Dysregulation of the profile of microRNAs (miRNAs) has been demonstrated in human tissues from PAH patients and in animal models. In this study, we measured miRNA levels in the monocrotaline (MCT) rat model of PAH and examined whether blocking a specific dysregulated miRNA not previously reported in this model, attenuated PAH. We also evaluated changes in miRNA expression in lung specimens from MCT PAH rats overexpressing human prostacyclin synthase, which has been shown to attenuate MCT PAH. METHODS: Expression levels of a panel of miRNAs were measured in MCT-PAH rats as compared to naïve (saline) control rats. Subsequently, MCT PAH rats were injected with a specific inhibitor (antagomiR) for miR-223 (A223) or a nonspecific control oligonucleotide (A-control) 4 days after MCT administration, then weekly. Three weeks later, RV systolic pressure and RV mass were measured. Total RNA, isolated from the lungs, microdissected pulmonary arteries, and right ventricle, was reverse transcribed and real-time quantitative PCR was performed. MiRNA levels were also measured in RNA isolated from paraffin sections of MCT-PAH rats overexpressing prostacyclin synthase. RESULTS: MiRs 17, 21, and 223 were consistently upregulated, whereas miRs 126, 145, 150, 204, 424, and 503 were downregulated in MCT PAH as compared to vehicle control. A223 significantly reduced levels of miR-223 in PA and lungs of MCT PAH rats as compared to levels measured in A-control or control MCT PAH rats, but A223 did not attenuate MCT PAH. Right ventricular mass and right ventricular systolic pressure in rats treated with A223 were not different from values in A-control or MCT PAH rats. In contrast, analysis of total RNA from lung specimens of MCT PAH rats overexpressing human prostacyclin synthase (hPGIS) demonstrated reversal of MCT-induced upregulation of miRs 17, 21, and 223 and an increase in levels of miR-424 and miR-503. Reduction in bone morphogenetic receptor 2 (BMPR2) messenger (m)RNA expression was not altered by A223, whereas human prostacyclin synthase overexpression restored BMPR2 mRNA to levels in MCT PAH to levels measured in naive controls. CONCLUSIONS: Inhibition of miR-223 did not attenuate MCT PAH, whereas human prostacyclin synthase overexpression restored miRNA levels in MCT PAH to levels detected in naïve rats. These data may establish a paradigm linking attenuation of PAH to restoration of BMPR2 signaling.

Pathological changes in pulmonary circulation in carbon tetrachloride (CCl4)-induced cirrhotic mice.

RATIONALE: Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease. OBJECTIVE: We investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH. METHODS AND RESULTS: Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery. CONCLUSION: Collectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions.

Attenuation of monocrotaline-induced pulmonary hypertension by luminal adeno-associated virus serotype 9 gene transfer of prostacyclin synthase.

Idiopathic pulmonary arterial hypertension (iPAH) is associated with high morbidity and mortality. We evaluated whether luminal delivery of the human prostacyclin synthase (hPGIS) cDNA with adeno-associated virus (AAV) vectors could attenuate PAH. AAV serotype 5 (AAV5) and AAV9 vectors containing the hPGIS cDNA under the control of a cytomegalovirus-enhanced chicken ß-actin (CB) promoter or vehicle (saline) were instilled into lungs of rats. Two days later, rats were injected with monocrotaline (MCT, 60 mg/kg) or saline. Biochemical, hemodynamic, and morphologic assessments were performed when the rats developed symptoms (3-4 weeks) or at 6 weeks. Luminal (airway) administration of AAV5 and AAV9CBhPGIS vectors (MCT-AAV5 and MCT-AAV9 rats) significantly increased plasma levels of 6-keto-PGF1(α) as compared with MCT-controls, and closely resembled levels measured in rats not treated with MCT (saline-saline). Right ventricular (RV)/left ventricular (LV)+septum (S) ratios and RV systolic pressure (RVSP) were greater in MCT-control rats than in saline-saline rats, whereas the ratios and RVSP in MCT-AAV5CBhPGIS and MCT-AAV9CBhPGIS rats were similar to saline-saline rats. Thickening of the muscular media of small pulmonary arteries of MCT-control rats was detected in histological sections, whereas the thickness of the muscular media in MCT-AAV5CBhPGIS and MCT-AAV9CBhPGIS rats was similar to saline-saline controls. In experiments with different promoters, a trend toward increased levels of PGF1(α) expression was detected in lung homogenates, but not plasma, of MCT-treated rats transduced with an AAV9-hPGIS vector containing a CB promoter. This correlated with significant reductions in the RV/LV+S ratio and RVSP in MCT-AAV9CBhPGIS rats that resembled levels in saline-saline rats. No changes in levels of PGF1(α), RV/LV+S, or RVSP were detected in rats transduced with AAV9-hPGIS vectors containing a modified CB promoter (CB7) or a distal epithelial cell-specific promoter (CC10). Thus, AAV9CBhPGIS vectors prevented development of MCT-induced PAH and associated pulmonary vascular remodeling.